The mouse placenta produces two placental lactogens: mouse placental lactogen-I (mPL-I) and mPL-II. The long-term objectives of the project are to understand what functions these hormones perform in various target tissues and to understand what regulates their production and concentrations in the fetal and maternal blood. Although relatively little is known at present about the biological activities and regulation of secretion of PLs in various species, it is clear from what is known, that PLs participate in several important processes during pregnancy, such as stimulating mammary gland differentiation, regulating maternal and fetal intermediary metabolism, and stimulating fetal growth. In the long term, investigating the physiology of PLs will contribute to a better understanding of the processes that influence fetal health and survival during pregnancy. The studies outlined in this renewal application are a continuation of previous work in this laboratory on the biological activity and regulation of secretion of mPL-I and mPL-II. A primary culture system will be developed for examining the regulation of mPL-I secretion. It will be used to screen mPL-I secretagogues. The biological activity of mPL-I will be examined with respect to its ability to inhibit prolactin surges in midpregnant mice, using recombinant mPL-I. The regulation of secretion of mPL-II will be examined in several series of experiments. The mechanism by which the pituitary gland suppresses the maternal serum mPL-II concentration will be investigated. A mPL-II-releasing factor present in the decidua will be purified and its physiology will be examined. Effects of gonadotropin-releasing hormone and growth hormone-releasing hormone on the synthesis and release of mPL-II and total placental proteins will be examined and the presence of these peptides in the mouse placenta will be investigated. The biological activity of mPL-II in the maternal mammary gland will be examined with respect to the stimulation of alpha- lactalbumin production. experiments will also be performed to identify proteins whose synthesis is stimulated by mPL-II in fetal mouse hepatocytes.